The University of Pennsylvania reflects a long tradition of multidisciplinary clinical and basic research in reproductive endocrinology, infertility, and reproductive biology. In the first sections of this application, we will provide a summary of the University's clinical and research activities in the area of reproductive medicine, review the available facilities, and focus on our capability to continue to participate in multi-center efforts to analyze and improve infertility management. The Penn RMU has been part of the RMN since the Network's inception over seventeen years ago and has played a leadership role in the design, implementation, analysis and publication of many of the RMN's studies. Specifically, of the three major studies the RMN has completed to date, two have been the proposed Penn concept protocols, one resulting in a NEJM publication and the second resulting in three Fertility and Sterility publications comprising the centerpiece of a Controversies section of the journal. These contributions have resulted in a change of the standard of care. In the present application, we propose the establishment of the Penn Reproductive Research Group (PRReG) in order to improve study subject recruitment in the greater Philadelphia area. In addition, the Penn concept protocol proposes to test the hypothesis that exposure of human embryos in vitro to reduced, more physiologic (5%) rather than supraphysiologic (20% - which is the standard of care) oxygen concentration improves live born rates. This is a randomized, double blind, multi-center clinical trial, which has the potential, based on existing animal data and preliminary human observations, to revolutionize the practice of assisted reproductive technologies. Following significant discussion, it was decided that an IVF- related protocol, in spite its politically charged nature, would be very important for the RMN to undertake since ART is central to current infertility treatments and since the RMN could be labeled "irrelevant" if it did not include an IVF project among its protocols. As designed, the proposed study does not utilize federal funds for any aspects of the human IVF work and, as such, makes it appropriate in the presence of current congressional restrictions. We strongly believe, that upon completion of the proposed study, the impact on current practice will be extremely significant. Given the track record, excellence of the clinical research infrastructure and the proven expertise in the design, recruitment and analysis of multi-center clinical trials, the members of the Penn RMU are looking forward to continue their participation in the Reproductive Medicine Network. [unreadable] [unreadable] [unreadable]